Effect of Glycine on the Induction of Orotic Aciduria and Urinary Bladder Tumorigenesis in the Rat

Abstract

The mechanism by which amino acids increase the cellular levels of orotic acid (OA) was investigated. Administration ofglycine (2.5 mmoles/100 g) to rats resulted in a 100-fold increase in urinary OA excretion, which was inhibited by pretreatment with cycloheximide or actinomycin D. The induction of OA synthesis from NH,Cl but not from carbamoylaspartate (CA) was inhibited by cycloheximide, indicating that the cycloheximide sensitive step was after the formation of ammonia and before the formation of CA. The glycine-stimulated OA synthesis was not inhibited by acivicin, a potent inhibitor of the cytosolic carbamoylphosphate (CP) synthctase, implicating the mitochondria1 CP synthetase in supplying the CP for OA synthesis. Preliminary results indicated that cycloheximide did not inhibit glycine-induced urea synthesis to any significant extent. The results thus suggest that (i) the increased OA synthesis induced by glycine requires a transcription-translation dependent step and (ii) the regulatory step may be the transport of mitochondria1 CP to cytosol and/or the synthesis of cytosolic CA. Attempts to determine whether increased exposure of urinary bladder to high concentrations of OA will influence bladder tumorigenesis revealed that chronic administration ofglycine (2.5 mmoles/lOO g, ip, daily, 5 days a week for 20 weeks) resulted in a 44% increased incidence of hyperplastic, preneoplastic, and neoplastic lesions. Some of these rats also exhibited stones in urinary bladders. The mechanism by which glycine induces tumorigenesis in the urinary bladder is currently being explored.

Efficiency of Hemodialysis of Pyrimidine Compounds in Patients with Chronic Renal Failure

“…It was found that the prolonged increase in orotic acid concentration in the body leads to lipid metabolism disorder and fatty infil tration of the liver [13,14], The role of orotic acid in promo tion of carcinogenesis has been recently reported [15,16].…”

Gold nanoparticles capped with L-glycine, L-cystine, and L-tyrosine: toxicity profiling and antioxidant potential

“…Cadmium ions lead to the activation of pro-survival signaling, which induce toxicity and tumors in the animal body [ 141 – 143 ]. Oratic acid is produced in excess amounts during the metabolism of glycine, which might play a role as a tumor promoter [ 144 ]. Zhang et al .…”

Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

“…This may discharge the variety of substances or other surgical procedures leading to urinary calculi in rats and/or mice. There were administered chemicals, acting directly (e.g., melamine) [40] or indirectly (i.e., through metabolites (diethylene glycol leading to calcium oxalate) [41] or through endogenous metabolic product (glycine leading to orotic acid) [42]) as well as the formation of urate calculi following surgical portocaval shunts in rats [43]). Also, in the rat vesciovaginal fistulas, like with the rat rectovaginal fistulas [10], the rat defect size/vaginal size ratio may be close to human disturbance (rectovaginal fistulas are con-˂ sidered complex if they are large ( 2.5 cm) [44]).…”